RESUMO
Background: Current phenotyping approaches for murine autism models often focus on one selected behavioral feature, making the translation onto a spectrum of autistic characteristics in humans challenging. Furthermore, sex and environmental factors are rarely considered. Here, we aimed to capture the full spectrum of behavioral manifestations in 3 autism mouse models to develop a "behavioral fingerprint" that takes environmental and sex influences under consideration. Methods: To this end, we employed a wide range of classical standardized behavioral tests and 2 multiparametric behavioral assays-the Live Mouse Tracker and Motion Sequencing-on male and female Shank2, Tsc1, and Purkinje cell-specific Tsc1 mutant mice raised in standard or enriched environments. Our aim was to integrate our high dimensional data into one single platform to classify differences in all experimental groups along dimensions with maximum discriminative power. Results: Multiparametric behavioral assays enabled a more accurate classification of experimental groups than classical tests, and dimensionality reduction analysis demonstrated significant additional gains in classification accuracy, highlighting the presence of sex, environmental, and genotype differences in our experimental groups. Conclusions: Together, our results provide a complete phenotypic description of all tested groups, suggesting that multiparametric assays can capture the entire spectrum of the heterogeneous phenotype in autism mouse models.
Traditional methods of studying behavior in mouse models of human disorders often focus on single behavioral features. The current study sought to address this gap by examining 3 autism mouse models, using a variety of traditional and novel behavioral tests and computational dimensionality reduction analyses, to create a "behavioral fingerprint" for each animal. This study also considered the effects of the environmental factor of housing conditions and sex on behavior in these models. The findings suggest that complex, multiparametric assays offer a more nuanced portrayal of behavioral variability in autism mouse models, showcasing the complex interplay of genetics, environment, and behavior.
RESUMO
Neuroscience lacks a diverse repertoire of model organisms, resulting in an incomplete understanding of the general principles of neural function. Ctenophores display many neurobiological and experimental features which make them a promising candidate to fill this gap. They possess a nerve net distributed across their body surface in the epithelial layer. There is a long-held assumption that nerve nets are "simple" and lack distinct organizational principles. We want to challenge this assumption and determine how stereotyped the structure of this network is. We estimated body surface area in Pleurobrachia pileus using custom optical projection tomography and light sheet morphometry imaging systems. Using an antibody against tyrosinated α-tubulin, we visualized the nerve net in situ and quantified the geometric properties using an automated segmentation approach. We characterized organizational rules of the epithelial nerve net in animals of different sizes and at different regions of the body. We found that specific morphological features within the nerve net are largely unchanged during growth. These properties must be essential to the functionality of the nervous system and therefore are maintained during a change in body size. We have also established the principles of organization of the network and showed that some of the geometric properties are variable across different parts of the body. This suggests that there may be different functions occurring in regions with different structural characteristics. This is the most comprehensive structural description of a ctenophore nerve net to date and demonstrates the amenability of P. pileus for whole organism network analysis.